Cancer is the second leading cause of death in the United States. Due to the ever increasing aging population in the United States, it is reasonable to expect that rates of cancer incidence will continue to grow. Cancer is currently treated using a variety of modalities including surgery, radiation therapy and chemotherapy. The choice of treatments depends upon the type, location and dissemination of the cancer. One of the advantages of surgery and radiation therapy is the ability to control to some extent the impact of the therapy, and thus to limit the toxicity to normal tissues in the body. Chemotherapy is arguably the most appropriate treatment for disseminated cancers such as leukemia and lymphoma as well as metastases. Chemotherapy is generally administered systemically and thus toxicity to normal tissues is a major concern. Not all tumors, however, respond to chemotherapeutic agents and others, although initially responsive to chemotherapeutic agents, may develop resistance. Thus there is a need for a better understanding of the mechanisms underlying the formation and progression of cancer and the development of resistance to treatment. There is also a need for more effective cancer treatments.
Evidence has accumulated over the past several years to support the hypothesis that angiogenesis promotes the growth and progression of solid tumors and leukemias. Angiogenesis favors the transition from hyperplasia to neoplasia i.e. the passage from a state of cellular multiplication to a state of uncontrolled proliferation characteristic of tumor cells. Angiogenesis also influences the dissemination of cancer cells throughout the entire body eventually leading to metastasis formation.
More recent evidence implicates angiogenesis in the pathogenesis of diseases other than cancer. For example, angiogenesis seems to provide a conduit for the entry of inflammatory cells into sites of chronic inflammation (e.g., Crohn's disease and chronic cystitis) and destroys cartilage in rheumatoid arthritis. Angiogenesis also contributes to growth and hemorrhage of atherosclerotic plaques, leads to intraperitoneal bleeding in endometriosis, and is a cause of blindness. Angiogenesis has also been implicated in the pathogenesis of other diseases and as a result the search for effective angiogenesis inhibitors has intensified. Several angiogenesis inhibitors have recently been discovered and some are currently in clinical trials.
Neuroblastoma is a leading cause of cancer death in children; it is the most common extracranial solid tumor in children, and it carries a poor prognosis. Current treatments of intensive chemotherapy, surgery, radiation and autologous bone marrow transplant are often unsuccessful leaving the patients uncured, weak, and unable to tolerate more intense treatment. Currently most children greater than 1 year of age fail standard therapies. Only 30% of these children survive up to 5 years after diagnosis1,2. New advancements in treatment strategies are therefore needed to improve the overall survival rate in neuroblastoma.